Abstract Number: PB0347
Meeting: ISTH 2020 Congress
Background: Factor VIII (FVIII) inhibitors remain the most significant complication of therapy in hemophilia A (HA), increasing both morbidity and mortality. Identification of molecular biomarkers of inhibitor development and/or persistence could aid in determining optimal therapy for HA inhibitor patients. Previously, we demonstrated that levels of the transitional B cell and plasma cell survival cytokines, B lymphocyte stimulator (BLyS) and B cell maturation antigen (BCMA), respectively, were elevated in a cohort of U.S. pediatric HA inhibitor patients. BLyS has been associated with high risk for auto-immune disease in Italy, raising whether levels may be elevated in Italian FVIII inhibitor patients.
Aims: Here, we investigated whether BLyS and BCMA levels were elevated in a cohort of Italian adult and pediatric HA with inhibitors.
Methods: Fifty HA patients were enrolled from the Careggi University Hospital hemophilia treatment center. Inhibitor titers were measured by Bethesda assay and BLyS and BCMA levels by a multiplex ELISA. BLyS and BCMA levels were compared by Mann-Whitney test. All studies were done according to Declaration of Helsinki and approved by Institutional Review Boards.
Results: Of 40 adult and 10 pediatric HA patients, 23 patients had no history of inhibitors, 5 had achieved FVIII tolerance, and 22 had an active inhibitor. The median age was 47.5 years (range 1-83) with no difference between those with and without inhibitors. Median BLyS levels were higher in inhibitor positive compared to inhibitor negative patients (1.13 vs 0.88 ng/ml, p=0.03, respectively) however BCMA levels were equal between the two cohorts (18.72 vs 19.34 ng/ml, p>0.05).
Conclusions: This study shows, for the first time, that elevated levels of BLyS are present in a cohort of Italian HA patients. As high BLyS has been described in auto- and allo-immune disease processes and targeted anti-BLyS therapy has been approved for lupus, these results further support anti-BLyS therapy for FVIII inhibitors.
To cite this abstract in AMA style:Doshi B, Castaman G, Arruda V. B Cell Cytokines in Italian Hemophilia A Patients with Inhibitors [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/b-cell-cytokines-in-italian-hemophilia-a-patients-with-inhibitors/. Accessed December 6, 2021.
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